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• W2125293856 abstract "ObjectiveViable motheaten mice (abbreviated gene symbol mev) are deficient in SHP-1, a critical negative regulator of signal transduction in hematopoietic cells. These mice exhibit severe immune dysfunction accompanied by hyperproliferation of myeloid cells, widespread inflammatory lesions, and regenerative anemia. The aim of this study was to investigate the mechanisms underlying anemia in mev/mev mice.Materials and MethodsMultiple hematologic parameters, osmotic fragility, and erythropoietin levels were measured to characterize the anemia in mev/mev mice. B-cell–deficient mev/mev Igh-6null mice were generated to assess the role of anti-erythrocyte antibodies. Coombs assays and flow cytometry were carried out for detection of anti-erythrocyte antibodies. Oxidant production by macrophages, glutathione levels, and lipid peroxidation products in erythrocytes were measured, as was the impact of oxidant on the ultrastructure of mev/mev erythrocytes. Erythroid maturation and erythrocyte plasma membrane integrity were assessed with flow cytometry by evaluating CD71 expression and annexin V labeling.ResultsThe regenerative anemia of mev/mev mice was associated with erythrocyte changes that were independent of the presence of anti-erythrocyte antibodies. Erythrocytes from mev/mev mice had increased fragility and heightened susceptibility to oxidant damage. Macrophages from mev/mev mice demonstrated a higher basal level of oxidant production and enhanced production after stimulation. Oxidant damage in mev/mev erythrocytes was evidenced by a significant elevation of lipid peroxidation and diminished levels of glutathione.ConclusionOur results support the hypothesis that as a consequence of severe inflammatory disease, mev/mev erythrocytes are subject to exceptionally high oxidative stress resulting in oxidation of phospholipids in the erythrocyte membrane with subsequent hemolysis." @default.
• W2125293856 created "2016-06-24" @default.
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• W2125293856 date "2003-03-01" @default.
• W2125293856 modified "2023-09-27" @default.
• W2125293856 title "Mechanisms of anemia in SHP-1 protein tyrosine phosphatase-deficient “viable motheaten” mice" @default.
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• W2125293856 doi "https://doi.org/10.1016/s0301-472x(02)01031-7" @default.
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